Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Agonist-stimulated divalent cation entry was studied in fura-2-loaded hepatocytes. In the presence of extracellular Mn2+, the Ca2(+)-mobilizing hormone vasopressin produced a severalfold stimulation of the basal rate of fura-2 fluorescence quenching as a result of Mn2+ influx; this effect was blocked by the presence of Ni2+ in the incubation medium. Half-maximum and maximum stimulation of Mn2+ influx was observed with 0.1 and 0.8 nM vasopressin, respectively. Agonist-stimulated Mn2+ influx was also seen with angiotensin II, ATP, phenylephrine, and the combination of AlCl3 and NaF. The stimulation of Mn2+ influx did not occur immediately after addition of Ca2(+)-mobilizing agents, but was characterized by a latency period of 20-30 s. In contrast to vasopressin, glucagon did not stimulate Mn2+ influx into hepatocytes, but produced both a 3-fold enhancement of the rate of vasopressin-stimulated Mn2+ entry and the abolishment of the latency period. The effects of glucagon were mimicked by forskolin and dibutyryl cAMP. Pretreatment of hepatocytes with pertussis toxin or depolarization of the cells altered neither the basal rate of Mn2+ entry nor the ability of vasopressin to stimulate this rate. Emptying of the inositol 1,4,5-trisphosphate-sensitive Ca2+ store by treatment with 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) did not enhance Mn2+ entry into hepatocytes; however, exposure of the cells to tBuBHQ for 2 min markedly enhanced the ability of vasopressin, alone or in combination with glucagon, to increase the rate of Mn2+ influx. Furthermore, pretreatment with tBuBHQ for 2 min abolished the latency of vasopressin-stimulated Mn2+ influx. It is concluded that Ca2(+)-mobilizing hormones stimulate Ca2+ influx in hepatocytes, possibly through receptor-operated Ca2+ channels. The stimulation of divalent cation entry is transduced by a G protein, and the rate of influx appears to be controlled both by the intracellular level of cAMP and the empty state of an intracellular Ca2+ pool that may be inositol 1,4,5-trisphosphate-insensitive.
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PMID:Receptor-operated calcium influx in rat hepatocytes. Identification and characterization using manganese. 217 Mar 82

In isolated guinea pig gastric chief cells, sodium fluoride (NaF) stimulated a monophasic increase in diacylglycerol accumulation, while cholecystokinin (CCK) strongly stimulated its biphasic accumulation. NaF evoked an increase in initial Ca2+ influx rate with a slow increase in intracellular free Ca2+ concentration [( Ca2+]i), while CCK stimulated a rapid increase in [Ca2+]i followed by a late sustained phase of the [Ca2+]i increase. Lanthanum chloride (La3+) effectively blocked NaF-stimulated increase in [Ca2+]i, but it blocked only CCK-stimulated late sustained phase of [Ca2+]i increase. The effect of NaF on pepsinogen secretion was enhanced in the presence of 100 microM AlCl3. Furthermore, pertussis toxin did not affect NaF-evoked diacylglycerol accumulation at all. These results suggest that NaF may activate a pertussis-toxin insensitive guanine nucleotide regulatory protein (G protein) coupled to a signal transducing mechanism which seems to be distinct from that activated by CCK, thereby inducing increases in diacylglycerol accumulation, Ca2+ influx and pepsinogen secretion in guinea pig gastric chief cells.
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PMID:Difference in effects of sodium fluoride and cholecystokinin on diacylglycerol accumulation and calcium increase in guinea pig gastric chief cells. 240 88

To clarify the possible role of a guanine nucleotide-binding protein (G protein) in the signal transducing system activated by cholecystokinin (CCK), actions of CCK on rat pancreatic acini were compared with those of fluoride, a well-known activator of stimulatory (Gs) or inhibitory (Gi) G protein. When acini were incubated with increasing concentrations of either CCK-octapeptide (CCK8) or NaF, a maximal stimulation of amylase release from acini occurred at 100 pM CCK8 or 10 mM NaF, respectively; this secretory rate decreased as CCK8 or NaF concentration was increased. NaF caused an increased in cytoplasmic Ca2+ concentration from the internal Ca2+ store and stimulated accumulation of inositol phosphates in acini, as observed with CCK. However, NaF-stimulated Ca2+ mobilization had a lag period before detectable stimulation and was potentiated by AlCl3. These stimulatory effects of NaF appeared to be independent of cellular adenosine 3',5'-cyclic monophosphate (cAMP). Pretreatment with cholera toxin or pertussis toxin did not affect CCK8- or NaF-induced inositol phosphate accumulation or Ca2+ mobilization. 5'-Guanylimidodiphosphate activated the generation of inositol phosphates in the [3H]inositol-labeled pancreatic acinar cell membrane preparation, with half-maximal and maximal stimulation at 1 and 10 microM, respectively. Furthermore, the effects of submaximal CCK concentrations on inositol phosphate accumulation in membranes were markedly potentiated in the presence of 100 microM GTP, which alone was ineffective. Combined findings of the present study strongly suggest that pancreatic CCK receptors are probably coupled to the activation of polyphosphoinositide (PI) breakdown by a G protein, which appears to be fluoride sensitive but is other than Gs- or Gi-like protein.
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PMID:G protein in stimulation of PI hydrolysis by CCK in isolated rat pancreatic acinar cells. 246 Oct 94

The effects of galanin (7-70 nM) on ATP-sensitive K+ channels (KATP channels), membrane potential and the release of insulin have been studied in the insulinoma cell line, RINm5F. Single-channel currents have been recorded from excised outside-out membrane patches as well as intact insulin-secreting cells and it is shown that galanin, added to the outside of the membrane, specifically activates KATP channels. Studies carried out using the fluorescent probe bisoxonol demonstrate that galanin hyperpolarizes RINm5F cells. Galanin was also found to abolish glyceraldehyde-stimulated immunoreactive insulin release from the insulinoma cells. Both the galanin-evoked hyperpolarization and inhibition of insulin release were abolished in cells pre-exposed to pertussis toxin. The possibility that the gating of KATP channels could be mediated by a G-protein was studied in patch-clamp experiments by adding F- to the solution bathing the inside of the cell membranes (open-cell), in order to generate the alumino-fluoride complex AlF4-. F- (1-10 mM) evoked dose-dependent activation of KATP channels and this effect was fully reversible. F- was also able to activate K+ channels inhibited by ATP. That the fluoride activation of KATP channels is mediated by the complex AlF4- was indicated by experiments in which AlCl3 (10 microM) was found to enhance further the activation of K+ channels evoked by 1 mM F- and by results showing that F(-)-stimulation of KATP channels was (i) abolished in the continued presence of F- by the Al3+ chelator deferoxamine (0.5 mM) and (ii) could be mimicked by VO4(3-) which has a structure similar to that of the AlF4- complex.
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PMID:Galanin activates nucleotide-dependent K+ channels in insulin-secreting cells via a pertussis toxin-sensitive G-protein. 247 May 86

The involvement of a guanine-nucleotide-binding regulatory protein (G protein) in the relaxing responses to adenosine receptor agonists was investigated in bovine coronary vessels. Ring segments of left anterior descending artery branches were suspended in organ baths for measurement of isometric tension. The adenosine analogs, 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD) caused concentration-dependent relaxations of coronary rings contracted with KCl. The relaxing effects of NECA and CAD were antagonized by the adenosine receptor antagonist 8-phenyltheophylline indicating the involvement of an adenosine receptor. In a separate series of experiments, incubation with cholera toxin inhibited the relaxing responses to NECA, CAD and isoproterenol but not those produced by sodium nitroprusside. Treatment with forskolin did not reduce the relaxing responses to NECA or CAD. N-ethylmaleimide and NaF/AlCl3 caused significant inhibition of the relaxations produced by both NECA and CAD. Incubation with pertussis toxin was without effect on relaxations induced by NECA and CAD. These results provide evidence for the involvement of G protein (possibly stimulatory G proteins) in the relaxing effects mediated by the bovine coronary artery adenosine receptor.
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PMID:Adenosine receptor-mediated relaxation in coronary artery: evidence for a guanyl nucleotide-binding regulatory protein involvement. 251 85

In isolated perfused rat hearts, epidermal growth factor (EGF; 15 nM) increased cellular cyclic AMP (cAMP) content by 9.5-fold. In rat cardiac membranes, EGF also stimulated adenylate cyclase activity in a dose-dependent manner, with maximal stimulation (35% above control) being observed at 10 nM-EGF. Half-maximal stimulation of adenylate cyclase was observed at 40 pM-EGF. Although the beta-adrenergic-receptor antagonist propranolol markedly attenuated the isoprenaline-mediated increase in cAMP content of perfused hearts and stimulation of adenylate cyclase activity, it did not alter the ability of EGF to elevate tissue cAMP content and stimulate adenylate cyclase. The involvement of a guanine-nucleotide-binding protein (G-protein) in the activation of adenylate cyclase by EGF was indicated by the following evidence. First, the EGF-mediated stimulation of adenylate cyclase required the presence of the non-hydrolysable GTP analogue, guanyl-5'-yl-imidodiphosphate (p[NH]ppG). Maximal stimulation was observed in the presence of 10 microM-p[NH]ppG. Secondly, in the presence of 10 microM-p[NH]ppG, the stable GDP analogue guanosine 5'-[beta-thio]diphosphate at a concentration of 10 microM blocked the stimulation of the adenylate cyclase by 1 nM- and 10 nM-EGF. Third, NaF + AlCl3-stimulated adenylate cyclase activity was not altered by EGF. The ability of EGF to stimulate adenylate cyclase was not affected by pertussis-toxin treatment of cardiac membranes. However, in cholera-toxin-treated cardiac membranes, when the adenylate cyclase activity was stimulated by 2-fold, EGF was ineffective. Finally, PMA by itself did not alter the activity of cardiac adenylate cyclase, but abolished the EGF-mediated stimulation of this enzyme activity. The experimental evidence in the present paper demonstrates, for the first time, that EGF stimulates adenylate cyclase in rat cardiac membranes through a stimulatory GTP-binding regulatory protein, and this effect is manifested in elevated cellular cAMP levels in perfused hearts exposed to EGF.
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PMID:Epidermal growth factor stimulates rat cardiac adenylate cyclase through a GTP-binding regulatory protein. 251 10

In mouse Balb/c3T3 fibroblasts, insulin-like growth factor (IGF)-II activates a calcium-permeable cation channel through a cell surface IGF-II receptor (Kojima, I., Nishimoto, I., Iiri, T., Ogata, E., and Rosenfeld, R. G. (1988) Biochem. Biophys. Res. Commun. 154, 9-19; Matsunaga, H., Nishimoto, I., Kojima, I., Yamashita, N., Kurokawa, K., and Ogata, E. (1988) Am. J. Physiol. 255, C442-C446). In the action of IGF-II, a pertussis toxin (or islet-activating protein; IAP)-sensitive GTP-binding protein (G protein) is inferred to be involved (Nishimoto, I., Hata, Y., Ogata, E., and Kojima, I. (1987) J. Biol. Chem. 262, 12120-12126). In the present study, we examined the direct coupling of the IGF-II receptor with G proteins. In broken Balb/c3T3 cell membranes, 10 nM IGF-II rapidly attenuated the IAP-catalyzed ADP-ribosylation of a 40-kDa protein in a manner requiring magnesium ion. The IGF-II-mediated attenuation in the IAP substrate activity was 80% recovered after washing off IGF-II and inhibited by coexisting guanosine 5'-O-(2-thiodiphosphate), while either aluminum fluoride solution (10 mM NaF plus 100 microM AlCl3) or 100 microM guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) reproduced the action of IGF-II. When purified IAP substrate G proteins (Gi1, Gi2, G0) were incubated with IGF-II in the presence of membranes from IAP-treated Balb/c3T3 cells, the attenuation in the IAP substrate activity was evident in Gi2, but not in Gi1 or G0. On the other hand, 10 nM insulin had no effect on the modification of the 40-kDa IAP substrate in Balb/c3T3 cell membranes, whereas 10 nM IGF-I elicited a slow onset of the IAP sensitivity attenuation from the 40-kDa protein. However, the specific involvement of the IGF-II receptor in the modification of the IAP substrate induced by low concentrations of IGF-II was suggested by the observations that (i) IGF-I receptor-lacking cell membranes were effective for the Gi2 modification by IGF-II, (ii) the ability of membranes to mediate the action of IGF-II was markedly attenuated in IGF-II receptor-lacking cell membranes, and (iii) agonistic anti-IGF-II receptor antibody mimicked the action of IGF-II on the 40-kDa protein in Balb/c3T3 cell membranes in a dose-dependent manner similar to that observed in the antibody-induced blocking of membrane IGF-II binding.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Possible direct linkage of insulin-like growth factor-II receptor with guanine nucleotide-binding proteins. 254 80

Treatment of hepatocytes with 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ), a novel mobilizer of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool, produces a sustained elevation of [Ca2+]i (Kass, G. E. N., Duddy, S. K., and Orrenius, S. (1989) J. Biol. Chem. 264, 15192-15198). Exposure of hepatocytes to the Ca2(+)-mobilizing hormones, vasopressin, angiotensin II, or ATP following [Ca2+]i elevation by tBuBHQ produced a rapid return of [Ca2+]i to basal or near basal levels. Release of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool by tBuBHQ following pretreatment with vasopressin or angiotensin II resulted in a [Ca2+]i transient and not the sustained [Ca2+]i elevation observed in the absence of the Ca2(+)-mobilizing hormones. The G-protein activator, NaF plus AlCl3, mimicked both effects of the Ca2(+)-mobilizing hormones on [Ca2+]i. The mechanism for Ca2+ removal from the cytosol by Ca2(+)-mobilizing hormones did not involve cyclic nucleotides nor did it require protein kinase C activation or cyclo- and lipoxygenase-dependent metabolites of arachidonic acid. Furthermore, the hormone-mediated decrease in [Ca2+]i did not involve the pertussis toxin-sensitive Gi-protein. Removal of the tBuBHQ-mobilized Ca2+ from the cytosol of hepatocytes by Ca2(+)-mobilizing hormones was mediated by stimulation of a Ca2+ efflux pathway. Thus, in addition to initiating [Ca2+]i transients by releasing Ca2+ from the inositol 1,4,5-trisphosphate-sensitive Ca2+ store and stimulating Ca2+ influx, Ca2(+)-mobilizing hormones also regulate the termination of the [Ca2+]i transient by stimulating a Ca2+ efflux pathway.
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PMID:Ca2(+)-mobilizing hormones stimulate Ca2+ efflux from hepatocytes. 255 86

The action of carbamoylcholine (Cchol), NaF and other agonists on the generation of inositol phosphates (IPs) was studied in dog thyroid slices prelabelled with myo-[2-3H]inositol. The stimulation by Cchol (0.1 microM-0.1 mM) of IPs accumulation through activation of a muscarinic receptor [Graff, Mockel, Laurent, Erneux & Dumont (1987) FEBS Lett. 210, 204-210] was pertussis- and cholera-toxin insensitive. Ins(1,4,5)P3, Ins(1,3,4)P3 and InsP4 were generated. NaF (5-20 mM) also increased IPs generation (Graff et al., 1987); this effect was potentiated by AlCl3 (10 microM) and unaffected by pertussis toxin. Although phorbol dibutyrate (5 microM) abolished the cholinergic stimulation of IPs generation (Graff et al., 1987), it did not affect the fluoride-induced response. Cchol and NaF did not require extracellular Ca2+ to exert their effect, and neither KCl-induced membrane depolarization nor ionophore A23187 (10 microM) had any influence on basal IPs levels, or on cholinergic stimulation. However, more stringent Ca2+ depletion with EGTA (0.1 or 1 mM) decreased basal IPs levels as well as the amplitude of the stimulation by Cchol without abolishing it. Dibutyryl cyclic AMP, forskolin, cholera toxin and prostaglandin E1 had no effect on basal IPs levels and did not decrease the response to Cchol. Iodide (4 or 40 microM) also strongly decreased the cholinergic action on IPs, this inhibition being relieved by methimazole (1 mM). Our data suggest that Cchol activates a phospholipase C hydrolysing PtdIns(4,5)P2 in the dog thyroid cell in a cyclic AMP-independent manner. This activation requires no extracellular Ca2+ and depends on a GTP-binding protein insensitive to both cholera toxin and requires no extracellular Ca2+ and depends on a GTP-binding protein insensitive to both cholera toxin and pertussis toxin. The data are consistent with a rapid metabolism of Ins(1,4,5)P3 to Ins(1,3,4)P3 via the Ins(1,4,5)P3 3-kinase pathway, followed by dephosphorylation by a 5-phosphomonoesterase. Indeed, a Ca2+-sensitive InsP3 3-kinase activity was demonstrated in tissue homogenate. Stimulation of protein kinase C and an organified form of iodine inhibit the Cchol-induced IPs generation. The negative feedback of activated protein kinase C could be exerted at the level of the receptor or of the receptor-G-protein interaction.
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PMID:Stimulation of generation of inositol phosphates by carbamoylcholine and its inhibition by phorbol esters and iodide in dog thyroid cells. 255 11

The effect of benzodiazepines on adenylate cyclase system was examined in rat brain. Micromolar concentrations of diazepam inhibited the enzyme activity in synaptic membranes in dose- and time-dependent manners. The inhibitory effect of diazepam was more evident on the enzyme activity in the presence of guanylyl-5'-imidodiphosphate (GppNHp) or NaF-AlCl3 than on that in the basal state. In the pertussis toxin-treated membranes, the effect of diazepam in the presence of GppNHp or NaF-AlCl3 was markedly suppressed. In addition, other benzodiazepines, such as medazepam, flurazepam, flunitrazepam, and clonazepam, had similar effects to those of diazepam, whereas Ro15-1788, an antagonist of a high affinity receptor in the central nervous system, had no effect on adenylate cyclase activity and did not antagonize the effect of diazepam. These findings indicate that benzodiazepines inhibit rat brain adenylate cyclase activity through the effects on both a low affinity benzodiazepine receptor coupled with the inhibitory GTP-binding regulatory protein (Gi) and catalytic protein.
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PMID:Inhibition of rat brain adenylate cyclase activity by benzodiazepine through the effects on Gi and catalytic proteins. 282 93


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